Structural basis for the recognition of sulfur in phosphorothioated DNA. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Liu, Guang; Fu, Wencheng; Zhang, Zhenyi; He, Yao; Yu, Hao; Wang, Yuli; Wang, Xiaolei; Zhao, Yi-Lei; Deng, Zixin; Wu, Geng; He, Xinyi
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 12
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-07093-1
• Languages: English
• ISSNs: 2041-1723

Abstract

Abstract There have been very few reports on protein domains that specifically recognize sulfur. Here we present the crystal structure of the sulfur-binding domain (SBD) from the DNA phosphorothioation (PT)-dependent restriction endonuclease ScoMcrA. SBD contains a hydrophobic surface cavity that is formed by the aromatic ring of Y164, the pyrolidine ring of P165, and the non-polar side chains of four other residues that serve as lid, base, and wall of the cavity. The SBD and PT-DNA undergo conformational changes upon binding. The S187 RGRR191 loop inserts into the DNA major groove to make contacts with the bases of the GPS GCC core sequence. Mutating key residues of SBD impairs PT-DNA association. More than 1000 sequenced microbial species from fourteen phyla contain SBD homologs. We show that three of these homologs bind PT-DNA in vitro and restrict PT-DNA gene transfer in vivo. These results show that SBD-like PT-DNA readers exist widely in prokaryotes. DNA phosphorothioation (PT-DNA) is a DNA backbone sulfur modification that is recognized by the type-IV restriction endonuclease ScoMcrA. Here the authors provide insights into sulfur recognition by solving the crystal structure of the PT-DNA bound sulfur-binding domain (SBD) from ScoMcrA and they further show that SBD homologs are widely spread among prokaryotes.